A deeper, mechanistic understanding of emotion-cognition interactions is likely to lead to major progress in the study and treatment of mental health. A first major goal of the proposed research is to investigate how approach-withdrawal states influence the neural substrates of high-level cognition, especially lateral pre-frontal cortex. A second major goal is to investigate individual differences in emotional reactivity and cognitive control function, because these are likely to influence emotion-cognition interactions. In previous work (PNAS; JEP: General) we have developed and validated a methodologically rigorous emotion-cognition challenge paradigm able to reveal a selective influence of induced emotional states (from short videos) on neural activity in dorsolateral PFC during a demanding task (verbal and nonverbal n-back tasks), which we will use to advantage in the current study. However, because high-order interactions can be hard to detect and individual differences may matter greatly, we strongly suspect that a typical neuroimaging study with a dozen or even 20 participants would be severely underpowered for our purposes. We propose to conduct an fMRI study with 100 healthy participants in that we collect diverse measures in a number of domains, including emotional states, cognitive function, personality, and whole-brain activity. We will measure both state-related and event-related neural activity, and conduct numerous in-depth analyses of these data using sophisticated analytic tools, including covariance-based methods. The exceptional statistical power (for an fMRI study) is absolutely crucial for the detection of what are likely to be subtle but important effects that could not otherwise be studied (such as personality or emotional state differences in effective connectivity, or Emotion x Cognition x Personality x Hemisphere interactions in brain activity). We will test several major hypotheses in a single dataset including tests of: three mechanisms by which affective states could modulate the neural bases of higher cognitive processes; prefrontal hemispheric differences in emotion; and biological models of personality and fluid intelligence. The results are likely to be of major theoretical and translational importance for the study and treatment of mental health and drug addiction.